State Key Laboratory of Virology/Institute of Medical Virology/Research Center of Food and Drug Evaluation/State Laboratory of Antiviral and Tumor of Traditional Chinese Medicine, School of Medicine, Wuhan University, Wuhan 430071, China.
Acta Pharmacol Sin. 2012 Dec;33(12):1533-41. doi: 10.1038/aps.2012.80. Epub 2012 Sep 3.
To study whether epigallocatechin gallate (EGCG), a green tea-derived polyphenol, exerted anti-influenza A virus activity in vitro and in vivo.
Madin-Darby canine kidney (MDCK) cells were tested. The antiviral activity of EGCG in the cells was determined using hemagglutination assay and qPCR. Time of addition assay was performed to determine the kinetics of inhibition of influenza A by EGCG. The level of reactive oxygen species (ROS) were determined with confocal microscopy and flow cytometry. BALB/c mice were treated with EGCG (10, 20 or 40 mg·kg(-1)·d(-1), po) for 5 d. On the 3rd d of the treatment, the mice were infected with influenza A virus. Histopathological changes, lung index and virus titers in the lungs were determined.
Treatment of influenza A-infected MDCK cells with EGCG (1.25-100 nmol/L) inhibited influenza A replication in a concentration-dependent manner (the ED(50) value was 8.71±1.11 nmol/L). Treatment with EGCG (20 nmol/L) significantly suppressed the increased ROS level in MDCK cells following influenza A infection. In BALB/c mice infected with influenza virus, oral administration of EGCG (40 mg·kg(-1)·d(-1)) dramatically improved the survival rate, decreased the mean virus yields and mitigated viral pneumonia in the lungs, which was equivalent to oral administration of oseltamivir (40 mg·kg(-1)·d(-1)), a positive control drug.
The results provide a molecular basis for development of EGCG as a novel and safe chemopreventive agent for influenza A infection.
研究表没食子儿茶素没食子酸酯(EGCG),一种绿茶来源的多酚,是否具有体外和体内抗甲型流感病毒活性。
检测 Madin-Darby 犬肾(MDCK)细胞。通过血凝试验和 qPCR 测定 EGCG 在细胞中的抗病毒活性。通过添加时间测定法确定 EGCG 抑制甲型流感的动力学。通过共聚焦显微镜和流式细胞术测定活性氧(ROS)水平。用 EGCG(10、20 或 40mg·kg(-1)·d(-1),po)处理 BALB/c 小鼠 5d。在治疗的第 3d,小鼠感染甲型流感病毒。测定肺组织的组织病理学变化、肺指数和病毒滴度。
用 EGCG(1.25-100nmol/L)处理感染甲型流感的 MDCK 细胞,以浓度依赖性方式抑制甲型流感复制(ED(50)值为 8.71±1.11nmol/L)。用 EGCG(20nmol/L)治疗可显著抑制甲型流感感染后 MDCK 细胞中 ROS 水平的升高。在感染流感病毒的 BALB/c 小鼠中,口服 EGCG(40mg·kg(-1)·d(-1))可显著提高存活率,降低平均病毒产量,并减轻肺部病毒性肺炎,与口服奥司他韦(40mg·kg(-1)·d(-1))相当,奥司他韦是一种阳性对照药物。
结果为将 EGCG 开发为新型、安全的甲型流感感染化学预防剂提供了分子基础。